BDI-fluorescence immunoassay: A rapid noninvasive oral cancer detection test.

About This Grant

Oral squamous cell carcinoma (OSCC) is rampant in low and middle-income countries where pathology reviews are often imprecise and misreported. In contrast, in oral primary care settings in higher-income countries, clinicians often perform biopsies with a high proportion—approximately 90%—yielding non-OSCC results. While reassuring for patients, this practice may contribute to increased healthcare costs, potential complications, and unnecessary stress. Therefore, a non-invasive chairside assay to discriminate OSCC from non-OSCC, within minutes, is a useful adjunct that could be used to determine if a patient requires a biopsy. We propose an innovative fluorescent immunoassay (FIA) rapid test based on a ratio of epithelial cell derived human beta defensins (hBDs) measured from oral tissue cytobrush samples, as a non-invasive adjunctive/screening tool to scalpel biopsy. We have extensively characterized hBDs; we were the first to describe their profiles in the oral cavity. They are small (~5kDa) antimicrobial and immunoregulatory peptides indigenous to the oral mucosa. We showed that hBD-3 promotes tumorigenesis and that cellular transformation at the early stages of OSCC leads to its overexpression with concomitant reduction of hBD-2; a finding confirmed by others. By exploiting this difference using our laboratory based ELISA platform (referred herein as BDI- ELISA), we were able to corroborate in blinded discovery and validation phase studies that the ratio of hBD- 3/hBD-2 isolated from cytobrush samples of lesion vs. contralateral normal tissue in the same patient, correlated with the diagnosis of OSCC. We refer to this ratio as the beta defensin index (BDI). Our I-Corp survey of primary care dental clinicians resulted in overwhelming preference for a chairside test over our BDI-ELISA test, as the former provides immediate information to the clinician to better advise the patient as to the urgency of the situation and motivates the patient towards an immediate follow-up biopsy. This has been shown to improve patient compliance and leads to faster intervention. Moreover, chairside testing is better suited for underserved communities where oral cancer rates are high. With the experience of having conducted a multi-institutional study to validate the BDI-ELISA, we are now well positioned, with our industrial partner Hemex Health Inc (Portland, OR), a leader in commercializing rapid point-of-care (POC) diagnostic devices in resource-limited settings, to manufacture (Aim 1), analytically test (Aim 2) and clinically validate the BDI-FIA-rapid test (Aim 3). Data showing that the BDI-FIA can detect recombinant hBD-2 and hBD-3 and in healthy and OSCC cytobrush samples with BDI scores is very encouraging. Successful completion of our Academic-Industrial Partnership R01 aims will lead to commercialization of BDI-FIA through the U.S. and Indian regulatory pathways. BDI-FIA will deliver chairside capability to clinicians in determining who needs a biopsy and will be a screening tool for OSCC in low-socio economic countries where oral cancer is highly prevalent, yet laboratory/pathology services are often lacking.